Prospective analysis of urokinase in the treatment of catheter sepsis in pediatric hematology-oncology patients

Abstract

Use of right atrial catheters (RACs) in children with cancer improves the comfort and efficacy of therapy. However, catheter-related infections are responsible for significant morbidity leading to the removal of approximately 20% of implanted RACs. Sepsis has been linked to thrombus and fibrin sheath formation within the RAC. Gram-negative and fungal infections appear to be particularly resistant to antibiotic therapy alone and most of these infections have required catheter removal. Urokinase has been effectively used for reopening thrombus occluded RACs. Theoretically, thrombolytic agents could improve the treatment of catheter-related infections by removing luminal sites of bacterial/fungal colonization. We prospectively monitored the use of urokinase and antibiotics for catheter-related sepsis in our pediatric hematology/oncology population from 1985 to 1991. Sepsis episodes were treated with 2 doses of urokinase and antibiotics (10 to 42 days) infused through the RAC. One to 2 mL of urokinase (5,000 U/mL) was instilled in the RAC for 1 hour, then removed and repeated 24 hours later. During the study, 224 RACs were placed in 177 children. RACs were in place for a total of 71,134 days (median, 274 days). There were 67 blood culture-positive sepsis episodes occurring in 50 RACs. Fifty-nine sepsis episodes were treated with urokinase and antibiotics and all responded by clearance of organisms from the blood. Three patients (5.1% of urokinase treated) had recurrent sepsis with the same organism within 2 months, were considered treatment failures and had RACs removed. Only 1 of 16 episodes of multiple organism/ Candida sepsis led to RAC removal due to inability to cure the infection. An additional patient died of leukemia and Candida pancreatic abscess. Two other RACs in the urokinase group were removed for subsequent exit site infections and one was removed due to a mechanical complication. A smaller subgroup of patients with 8 catheter sepsis episodes were treated with antibiotics alone. In this group, one RAC required removal due to persistent infection, 2 patients died with infection and disease relapse, and 2 catheters were removed before completing antibiotic therapy. The remaining 3 patients retained their RAC. Isolated exit site or tunnel infections without bacteremia were observed on 8 occasions and lead to the removal of 6 RACs. Overall, only 13 of 224 RACs (5.8%) were removed due to all catheter-related infections. No adverse effects of urokinase instillation were observed. The concomitant use of urokinase and antibiotics can effectively and safely treat catheter-related sepsis leading to salvage of over 90% of infected RACs. This protocol is not designed for improvement of RAC exit site infection therapy.